rs1148259

Positions:

• chr10-37219522-A-C
• chr10-37219522-A-G
• chr10-37219522-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052997.3(ANKRD30A):​c.3810A>C​(p.Ala1270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,609,586 control chromosomes in the GnomAD database, including 170,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15377 hom., cov: 31)
  • Exomes 𝑓: 0.45 (154728 hom.)
• Consequence: ANKRD30A NM_052997.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

ANKRD30A (HGNC:17234): (ankyrin repeat domain 30A) This gene encodes a DNA-binding transcription factor that is uniquely expressed in mammary epithelium and the testis. Altered expression levels have been associated with breast cancer progression. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-0.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD30A	NM_052997.3	c.3810A>C	p.Ala1270=	synonymous_variant	34/36	ENST00000361713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD30A	ENST00000361713.2	c.3810A>C	p.Ala1270=	synonymous_variant	34/36	5	NM_052997.3	A2
ANKRD30A	ENST00000374660.7	c.4167A>C	p.Ala1389=	synonymous_variant	40/42	5		P4
ANKRD30A	ENST00000602533.7	c.3810A>C	p.Ala1270=	synonymous_variant	34/36	5		A2
ANKRD30A	ENST00000696674.1	c.543A>C	p.Ala181=	synonymous_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67001 AN: 150582 Hom.: 15376 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.432

GnomAD3 exomes AF: 0.497 AC: 122906 AN: 247228 Hom.: 32053 AF XY: 0.505 AC XY: 67842 AN XY: 134256

Gnomad AFR exome AF: 0.395

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.468

Gnomad EAS exome AF: 0.660

Gnomad SAS exome AF: 0.720

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.453 AC: 660365 AN: 1458886 Hom.: 154728 Cov.: 67 AF XY: 0.461 AC XY: 334364 AN XY: 725738

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.691

Gnomad4 SAS exome AF: 0.717

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.445 AC: 67027 AN: 150700 Hom.: 15377 Cov.: 31 AF XY: 0.452 AC XY: 33263 AN XY: 73634

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.436

Alfa AF: 0.429 Hom.: 7634

Bravo AF: 0.434

Asia WGS AF: 0.668 AC: 2321 AN: 3478

EpiCase AF: 0.436

EpiControl AF: 0.436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.89
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1148259; hg19: chr10-37508450; COSMIC: COSV64624907;